L4 - Calcium Homeostasis Flashcards
(14 cards)
The importance of calcium (7)
- Vital organ protection: Skull, Ribcage
- Movement: Long bones & Skeletal Muscle Contraction (shorten)
- Neurotransmitter release (influx for vesicle)
- CV system: Cardiac & SM Contraction
- Hormone secretion
- Blood clotting
- Intracellular signalling: Ca2+i oscillations, apoptosis
Plasma Ca2+ - soluble & insoluble (%’s and detection)
- Total plasma Ca2+ levels ~ 2.5 mM (10mg/dl) - unbound?
- ~40% bound to macromolecular proteins, e.g. albumin. (out of solution) – not free ionized
- ~5% complexed as Ca2+ salts e.g. bicarbonate, phosphate (kept low as can crystalize in blood)
- Thus, free ionised Ca2+ concentration is ~ 1.2 mM.
- Can only detect unbound calcium
Calciotropic Hormones (4)
- Parathyroid Hormone
- Vitamin D (1,25[OH]2D3)
- Calcitonin
- Extracellular Calcium (not really a hormone but does travel in blood stream and effects target cells – maybe a first messenger)
Parathyroid Gland (no of glands, work where)
• Ivar Sandstrom
• % of people > four glands.
o Some have 2 to 6 – mainly in even numbers.
• As long as they can regulate calcium the no. doesn’t matter
• Fish gills also express PTH 1/2-encoding genes in fish and CaR
• Thus, PT glands are in the neck because they are derived from gill
o Can place glands anywhere in the body (e.g. arms) and work perfectly)
Parathyroid Hormone (PTH) (produced where, other name and aa length)
- Produced in Chief cells of Parathyroid gland.
- Sometimes referred to as parathormone
- 84 aa hormone (t1/2 < 20 mins)
Relationship of extracellular Ca2+ and PTH
• PTH secretion is inversely proportional to serum Ca2+
o Low plasma [Ca2+] → ↑ PTH secretion
o High plasma [Ca2+] → ↓ PTH secretion
Effects of PTH: elevates plasma Ca2+ levels by: Bone (new bone, balance and tyope of reacton)
↑ Bone resorption
• New bones – calcium (mineral) and space to put it in (need to break down old bone)
• Balanced PTH secretion healthy – constant high levels are bad as it breaks down bone
• Catabolic first then anabolic
Effects of PTH: elevates plasma Ca2+ levels by: ↑ Renal (reabsorbtion/excretion, where and how much is excreted)
↑ Renal Ca2+ reabsorption i.e. ↓excretion (but also ↑Pi excretion)
• PTH decrease excretion to increase calcium reabsorption but increase Pi excretion
• Nefron – most absorption in the proximal tubule (70%) = mass not very regulated
o Control reabsorption in the thick ascending limb (20%) calcium receptors
o 9% in distal – vitamin D receptors and 1% in urine
facts of PTH: elevates plasma Ca2+ levels by: Production of 1,25(OH)2D3 (Vit D) (what 2 things does it increase and where)
↑ Production of 1,25(OH)2D3 (Vit D)
• Vitamin D (1,25(OH)2D3) production
o 1,25(OH)2D3 ↑ net intestinal Ca2+ uptake
o 1,25(OH)2D3 ↑ serum Ca2+ levels by ↑ bone resorption and renal Ca2+ reabsorption (as for PTH).
• In liver (25) unregulated/constitutively hydrozylated
• Second hydroxylation in kidney (proximal tubule)
Intestinal Ca2+ absorption and TRP (% and 2 types of transport, TRP effect on membrane)
90% of dietary Ca2+ absorption occurs in the small intestine via a) passive, paracellular diffusion down its electrochemical gradient, and, b) by active transcellular transport under the control of 1,25(OH)2D3.
TRP channels causes holes (open channel and calcium enter) apoptosis can happen (signal) with this influx – enzymes begin to run out of ATP to pump calcium out (basal/cytosolic) and drives cell death. Calbindind (cytosolic binding protein) bind to calcium and therefore no longer in solution and pumped out the cell (need PMCA and NCX? And use ATP) – This is active and passive can occur but insufficient to avoid illness/rickets
Calbindins (2 sizes/locations and other facts)
• Calbindin
o D28K, mainly present in kidney
o D9K, expressed primarily in gut
• Reabsorptive epithelia need protection from mM Ca2+ crossing cell [Ca2+]i ~ 10pM
• Calbindin expression substantially dependent on 1,25(OH)2D3
Calcitonin (size, secreted from.., proportion compared to Ca)
• 32 aa peptide (from pro-calcitonin)
• Secreted from Parafollicular thyroidal “C cells”
• t1/2 5 min
• Calcitonin (CT) ↓ plasma Ca2+ following a Ca2+ load
o ↓ osteoclast activity → ↓bone resorption → allowing rapid bone deposition
• CT secretion rises post-prandially as blood Ca2+ rises, (gastrin may be involved in this secretion) and is inhibited by LOW Ca2+ levels in the blood
• Contribution of CT to mammalian calcium homeostasis is very modest & «_space;than in fish
o No known diseases associated to humans
Diseases of Calcium Homeostasis
• Primary Hyperparathyroidism
o Secondary Hyperparathyroidism (Renal Failure)
• Osteoporosis
• Rickets (Vit D deficiency/1aOHase mutation)
• Calcium Stones
• Receptor Mutations: PTH receptor, CaR
Space Travel & Calcium Homeostasis
• Bone demineralisation – a major physiological problem for spaceflight, esp. to Mars.
• Microgravity:
o ↑ bone resorption
o ↑ hypercalciuria & hyperphosphaturia
o ↑ risk renal stones.
• Also, 20M Americans have nephrolithiasis.
